Migration of germline progenitor cells is directed by sphingosine-1-phosphate signalling in a basal chordate

Kassmer, Susannah H.; Rodriguez, Delany; Langenbacher, Adam D.; Bui, Connor; Tomaso, Anthony W. De

doi:10.1038/ncomms9565

Cited by 43 publications

(81 citation statements)

References 33 publications

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“…In Botryllus schlosseri, we had previously identified a population of germline stem cells (GSCs) that expresses integrin-alpha-6 and vasa [17]. GSCs are found in germline niches in the developing zooids, as well as in the blood.…”

Section: Resultsmentioning

confidence: 99%

“…In Botryllus schlosseri, germline stem cells are a population of hemoblasts that give rise to gonads during asexual reproduction (palleal budding), whereas all somatic tissues are derived from the parent zooids peribranchial epithelium and not from blood borne cells [14]. In a previous study, we have shown that IA6 is expressed on vasa+ GSC in Botryllus schlosseri [44]. In future studies, we will investigate the similarities and differences between IA6+cells from Botrylloides and from B. schlosseri.…”

Section: Discussionmentioning

confidence: 97%

“…The cells express genes associated with germ cells, such as vasa, piwi and pumilio [12,13,16]. We have previously shown that in Botryllus schlosseri, a population of cells enriched for expression of these germline genes can be prospectively isolated based on expression of Integrin-alpha-6 (IA6) [17]. Vasa and piwi are part of the germline multipotency program [18], and IA6 is a biomarker for various kinds of mammalian stem cells, including embryonic stem cells and primordial stem cells [19].…”

mentioning

confidence: 99%

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Integrin-alpha-6+ Stem Cells (ISCs) are responsible for whole body regeneration in an invertebrate chordate

Kassmer¹,

Langenbacher²,

Tomaso³

2019

Preprint

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Colonial ascidians such as Botrylloides are the only chordates able to undergo whole body regeneration (WBR), during which entire new bodies can be regenerated from small fragments of blood vessels. Although it has long been suspected that undifferentiated blood borne cells called hemoblasts play an important role, the cellular and molecular mechanisms of this regeneration process are poorly understood. Here, we show that during the early stages of WBR, proliferation occurs only in small, blood borne cells that express integrin-alpha-6, pou3 and vasa. Proliferating cells can be ablated using Mitomycin C (MMC), leading to loss of WBR. However, regeneration can be rescued by injection of blood cells from a healthy individual into MMC treated vessel fragments. Using FACS-based prospective isolation, we found that injection of a single Integrin-alpha-6 (IA6)-positive cell is capable of rescuing WBR. Lineage tracing using EdU-labeling further revealed that IA6+ cells give rise to regenerating tissues. Our data suggest that ia6+pou3+ cells are proliferating blood borne stem cells that are responsible for whole body regeneration. IA6+ Stem Cells (ISCs) also express notch and frizzled receptors, and inhibitors of either Notch or canonical Wnt signaling block WBR and reduce proliferation, indicating that these two pathways regulate ISC activation.These results provide important insights into the mechanisms and evolution of chordate regeneration.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 97%

mentioning

confidence: 99%

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Integrin-alpha-6+ Stem Cells (ISCs) are responsible for whole body regeneration in an invertebrate chordate

Kassmer¹,

Langenbacher²,

Tomaso³

2019

Preprint

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“…As there are multiple targets downstream FTY720/S1PRs, it is not clear which signal pathway underlies the mechanism. Recently, Kassmer et al reported that the migratory response of germline progenitor cells is dependent on activation of PI3K and Rac1 downstream of the S1P1 [33]. This G-protein-coupled receptors mediate cellular responses to attractive chemokines in a variety of cell types, including NSCs.…”

Section: Discussionmentioning

confidence: 99%

Effects of FTY720 (Fingolimod) on Proliferation, Differentiation, and Migration of Brain‐Derived Neural Stem Cells

Tan

Luo

Yan

et al. 2016

Stem Cells International

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Insufficient proliferation, differentiation, and migration are the main pitfalls of neural stem cells (NSCs) in reparative therapeutics for the central nervous system (CNS) diseases. The potent lipid mediator sphingosine-1-phosphate (S1P) regulates cells' biological behavior broadly in the CNS. However, the effects of activating S1P on NSCs are not quite clear. In the current study, FTY720 (Fingolimod), an analog of S1P, was employed to induce the proliferation, differentiation, and migration of cultured brain-derived NSCs. The results indicated that proliferation and migration ability of NSCs were promoted by FTY720. Though we observed no obvious neuron prefers differentiation of NSCs, there were more protoplasmic astrocytes developed in the presence of certain concentration of FTY720. This work gives more comprehensive understanding of how FTY720 affects NSCs.

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“…However, this mechanism appears to be conserved, as LPPs also repel germ cells away from nearby somites in the zebrafish 6 . Recently, our group discovered that migration of germ cells is directed by the lysophospholipid Sphingosine-1-phosphate (S1P) in the colonial ascidian Botryllus schlosseri 7 .…”

Section: Introductionmentioning

confidence: 99%

ABC-transporter activity and autocrine eicosanoid-signaling are required for germ cell migration a basal chordate

Kassmer¹,

Rodriguez²,

DeTomaso³

2018

Preprint

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In the colonial ascidian Botryllus schlosseri, long-lived germline stem cells (GSCs) migrate to new germline niches as they develop during repetitive cycles of asexual reproduction. ABC-transporters are involved in the export of lipid-signaling molecules, but their roles in germ cell migration are poorly understood. Here, we show that in Botryllus, abcc1 and abcb1 are highly expressed in germ cells, and inhibition of ABCtransporter activity leads to failure of germ cell migration. Phospholipase A2 (PLA2) produces arachidonic acid, which is further metabolized to eicosanoid signaling molecules. In humans, 12-lipoxygenase (LOX) metabolizes arachidonic acid to12-Hydroxyeicosatetraenoic acid (12-S-HETE), which stimulates migration of mammalian cancer cells and smooth muscle cells. We show that PLA2 and LOX activity are required for germ cell migration. A potential homolog to the human receptor for 12-S-HETE, BSgpr31, is expressed in germ cells. 12-S-HETE rescues migration towards S1P in the presence of inhibitors of ABCC1, ABCB1, PLA2 or LOX, and a gradient of 12-S-HETE enhances chemotaxis towards S1P and stimulates motility. We conclude that 12-S-HETE is a secondary chemoattractant exported by ACB-transporters that is required for migration of germ cells towards S1P. We also find that in the presence of S1P, detection of an 12-S-HETE gradient initiates an autologous positive feedback loop that may sustain migration. This is the first report of an eicosanoid-signaling molecule regulating germ cell migration.

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Migration of germline progenitor cells is directed by sphingosine-1-phosphate signalling in a basal chordate

Cited by 43 publications

References 33 publications

Integrin-alpha-6+ Stem Cells (ISCs) are responsible for whole body regeneration in an invertebrate chordate

Integrin-alpha-6+ Stem Cells (ISCs) are responsible for whole body regeneration in an invertebrate chordate

Effects of FTY720 (Fingolimod) on Proliferation, Differentiation, and Migration of Brain‐Derived Neural Stem Cells

ABC-transporter activity and autocrine eicosanoid-signaling are required for germ cell migration a basal chordate

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